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Archives of Toxicology

, Volume 92, Issue 3, pp 1267–1281 | Cite as

Transcriptome profile analysis reveals cardiotoxicity of maduramicin in primary chicken myocardial cells

  • Xiuge Gao
  • Lin Peng
  • Xiangchun Ruan
  • Xin Chen
  • Hui Ji
  • Junxiao Ma
  • Han Ni
  • Shanxiang Jiang
  • Dawei Guo
Organ Toxicity and Mechanisms

Abstract

Maduramicin, an excellent ionophore antibiotic, is extensively used to control coccidiosis in poultry. Numerous maduramicin intoxications have been reported in farm animal and human due to its relatively narrow safety range, with necrosis or degeneration of cardiac and skeletal muscles as hallmark. To date, the mechanisms of maduramicin-induced cardiotoxicity remain unclear in chicken and other animals. Maduramicin (5 µg/mL)-treated primary chicken myocardial cells were used for RNA sequencing (RNA-Seq) and bioinformatics analysis in this study. A total of 1442 differential expressed genes were identified. 810 genes were up-regulated and the rest 632 genes were down-regulated. Transcriptome analysis revealed that the cytokine–cytokine receptor interaction, apoptosis, calcium signal and cytoplasmic vacuolization pathways were significantly affected. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis showed that gene expression patterns were consistent with RNA-Seq analysis. Pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8), apoptosis ratios, cleaved caspase-3, intracellular calcium level and Ca2+-ATPase activity were elevated after maduramicin (0.05, 0.5 and 5 µg/mL) treatment. Massive vacuole formation was found in the cytoplasm by morphology and transmission electron microscopy observation. Taken together, the results suggested that maduramicin exerted its cardiotoxicity by multiple molecular mechanisms in primary chicken myocardial cells.

Keywords

Transcriptome Bioinformatics analysis Maduramicin Cardiotoxicity Chicken myocardial cells 

Notes

Acknowledgements

The authors would like to acknowledge the assistance of Prof. Dr. Long Chen and Shile Huang. We also thank Jinhu Huang, Tengfei Liu, Yun Hu and Zohaib Ahmed Bhutto for helpful comments on the manuscript. This work was supported by grants from the National Natural Science Foundation of China (31672612, 31502120), the National Key Research and Development Program (2016YFD0501306) and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

204_2017_2113_MOESM1_ESM.rar (1.5 mb)
Supplementary material 1 (RAR 1500 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Xiuge Gao
    • 1
  • Lin Peng
    • 1
  • Xiangchun Ruan
    • 1
    • 2
  • Xin Chen
    • 3
  • Hui Ji
    • 1
  • Junxiao Ma
    • 1
  • Han Ni
    • 1
  • Shanxiang Jiang
    • 1
  • Dawei Guo
    • 1
  1. 1.Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary MedicineNanjing Agricultural UniversityNanjingPeople’s Republic of China
  2. 2.Laboratory of Veterinary Pharmacology and Toxicology, College of Animal Science and TechnologyAnhui Agricultural UniversityHefeiPeople’s Republic of China
  3. 3.Postdoctoral Mobile Station of Biology, College of Life SciencesNanjing Normal UniversityNanjingPeople’s Republic of China

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